Targeting the Bcl-2 family and P-glycoprotein reverses paclitaxel resistance in human esophageal carcinoma cell line

Shi, Xiaoli; Dou, Yinhui; Zhou, Kairui; Huo, Jin-Ling; Yang, Tengjiao; Qin, Tiantian; Liu, Weihua; Wang, Saiqi; Yang, Dongxiao; Chang, Liming; Wang, Cong

doi:10.1016/j.biopha.2017.04.043

Cited by 27 publications

(11 citation statements)

References 30 publications

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“…Currently, Taxol is widely used in the treatment of NSCLC in the clinics. However, many patients have acquired resistance to Taxol, and even those who initially respond will eventually exhibit MDR . We have confirmed that BZML has potent anti‐cancer activity against Taxol‐sensitive or Taxol‐resistant A549 cells through different death modes in vitro .…”

Section: Discussionsupporting

confidence: 54%

“…However, many patients have acquired resistance to Taxol, and even those who initially respond will eventually exhibit MDR. [44][45][46][47] We have confirmed that BZML has potent anti-cancer activity against Taxol-sensitive or Taxol-resistant A549 cells through different death modes in vitro. 10 This paper aimed to evaluate the anticancer activity of BZML in vivo and the mechanism underlying the apoptosis resistance in BZML-treated A549/Taxol cells.…”

Section: Discussionmentioning

confidence: 52%

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Overcoming resistance to mitochondrial apoptosis by BZML‐induced mitotic catastrophe is enhanced by inhibition of autophagy in A549/Taxol cells

Bai

Gao

et al. 2018

Cell Proliferation

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Section: Discussionsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 52%

Overcoming resistance to mitochondrial apoptosis by BZML‐induced mitotic catastrophe is enhanced by inhibition of autophagy in A549/Taxol cells

Bai

Gao

et al. 2018

Cell Proliferation

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“…So far, the signaling link between DKK3 and P-glycoprotein has not been elucidated. P-glycoprotein, acting as an ATP-dependent efflux pump, transports various chemo agents, such as paclitaxel, to outside the cells, which is a well-known mechanism of drug resistance [ 21 , 22 , 23 , 43 ]. Previous studies have shown that adenovirus-DKK3 treatment suppressed P-glycoprotein expression in an Akt/NFκB or c-Jun-kinase (JNK)-dependent manner [ 8 , 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

DKK3, Downregulated in Invasive Epithelial Ovarian Cancer, Is Associated with Chemoresistance and Enhanced Paclitaxel Susceptibility via Inhibition of the β-Catenin-P-Glycoprotein Signaling Pathway

Nguyen

Park

Lee

et al. 2022

Cancers

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Dickkopf-3 (DKK3), a tumor suppressor, is frequently downregulated in various cancers. However, the role of DKK3 in ovarian cancer has not been evaluated. This study aimed to assess aberrant DKK3 expression and its role in epithelial ovarian carcinoma. DKK3 expression was assessed using immunohistochemistry with tissue blocks from 82 patients with invasive carcinoma, and 15 normal, 19 benign, and 10 borderline tumors as controls. Survival data were analyzed using Kaplan–Meier and Cox regression analysis. Paclitaxel-resistant cells were established using TOV-21G and OV-90 cell lines. Protein expression was assessed using Western blotting and immunofluorescence analysis. Cell viability was assessed using the MT assay and 3D-spheroid assay. Cell migration was determined using a migration assay. DKK3 was significantly downregulated in invasive carcinoma compared to that in normal, benign, and borderline tumors. DKK3 loss occurred in 56.1% invasive carcinomas and was significantly associated with disease-free survival and chemoresistance in serous adenocarcinoma. DKK3 was lost in paclitaxel-resistant cells, while β-catenin and P-glycoprotein were upregulated. Exogenous secreted DKK3, incorporated by cells, enhanced anti-tumoral effect and paclitaxel susceptibility in paclitaxel-resistant cells, and reduced the levels of active β-catenin and its downstream P-glycoprotein, suggesting that DKK3 can be used as a therapeutic for targeting paclitaxel-resistant cancer.

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“…For example, CCND1 overexpression promotes paclitaxel-induced apoptosis in breast cancer 26 . BCL-2 family members such as BCL-2, BCl-xL, BAX, and ABCB1, have been reported to be involved in paclitaxel resistance in esophageal cancer 27 . In addition, SPARC expression in tumor stromal cells is a potential negative predictor of paclitaxel treatment in patients with lung cancer 28 , 29 .…”

Section: Discussionmentioning

confidence: 99%

Gastric cancer biomarker analysis in patients treated with different adjuvant chemotherapy regimens within SAMIT, a phase III randomized controlled trial

Oshima

Tsuburaya²,

Yoshida

et al. 2022

Sci Rep

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Biomarkers for selecting gastric cancer (GC) patients likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy (sequential paclitaxel) were investigated using tissue samples of patients recruited into SAMIT, a phase III randomized controlled trial. Total RNA was extracted from 556 GC resection samples. The expression of 105 genes was quantified using real-time PCR. Genes predicting the benefit of sequential paclitaxel on overall survival, disease-free survival, and cumulative incidence of relapse were identified based on the ranking of p-values associated with the interaction between the biomarker and sequential paclitaxel or monotherapy groups. Low VSNL1 and CD44 expression predicted the benefit of sequential paclitaxel treatment for all three endpoints. Patients with combined low expression of both genes benefitted most from sequential paclitaxel therapy (hazard ratio = 0.48 [95% confidence interval, 0.30–0.78]; p < 0.01; interaction p-value < 0.01). This is the first study to identify VSNL1 and CD44 RNA expression levels as biomarkers for selecting GC patients that are likely to benefit from sequential paclitaxel treatment followed by fluorinated-pyrimidine-based adjuvant chemotherapy. Our findings may facilitate clinical trials on biomarker-oriented postoperative adjuvant chemotherapy for patients with locally advanced GC.

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Targeting the Bcl-2 family and P-glycoprotein reverses paclitaxel resistance in human esophageal carcinoma cell line

Cited by 27 publications

References 30 publications

Overcoming resistance to mitochondrial apoptosis by BZML‐induced mitotic catastrophe is enhanced by inhibition of autophagy in A549/Taxol cells

Overcoming resistance to mitochondrial apoptosis by BZML‐induced mitotic catastrophe is enhanced by inhibition of autophagy in A549/Taxol cells

DKK3, Downregulated in Invasive Epithelial Ovarian Cancer, Is Associated with Chemoresistance and Enhanced Paclitaxel Susceptibility via Inhibition of the β-Catenin-P-Glycoprotein Signaling Pathway

Gastric cancer biomarker analysis in patients treated with different adjuvant chemotherapy regimens within SAMIT, a phase III randomized controlled trial

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